Characterization of Clinical Cases of Collecting Duct Carcinoma of the Kidney Assessed by Comprehensive Genomic Profiling

Pal, Sumanta K.; Choueiri, Toni K.; Wang, Kai; Khaira, Depinder; Karam, Jose A.; Allen, Eliezer Van; Palma, Norma Alonzo; Stein, Mark N.; Johnson, Adrienne; Squillace, Rachel M.; Elvin, Julia A.; Chmielecki, Juliann; Yelensky, Roman; Yakirevich, Evgeny; Lipson, Doron; Lin, Douglas I.; Miller, Vincent A.; Stephens, Philip J.; Ali, Siraj M.; Ross, Jeffrey S.

doi:10.1016/j.eururo.2015.06.019

Cited by 96 publications

(63 citation statements)

References 31 publications

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“…By comparison, in collecting duct carcinoma, which is morphologically similar to RMC, only infrequent truncating mutations in SMARCB1 have been seen (18% of tumors in a series). 18 Next-generation sequencing revealed no additional recurrent mutations in matched tumor and normal samples. This finding is in concordance with a previously published report of 5 cases of RMC, in which 4 tumors harbored translocations, and a fifth tumor showed biallelic loss.…”

Section: Discussionmentioning

confidence: 94%

Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes

Carlo

Chaim

Patil

et al. 2017

Clinical Genitourinary Cancer

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Background Renal medullary carcinoma (RMC) is a rare and aggressive type of kidney cancer that primarily affects young adults with sickle cell trait; outcomes are poor despite treatment. Identifying molecular features of this tumor could provide biologic rationale for novel targeted therapies. The objective was to report on clinical outcomes with systemic therapy and characterize molecular features. Patients and Methods This was a retrospective analysis on 36 patients given a pathologic diagnosis of RMC at one institution from 1995 to 2015. Tumors were analyzed for expression of SMARCB1 through immunohistochemistry and for genomic alterations with fluorescence in situ hybridization for SMARCB1, and targeted next-generation sequencing. Time from initiation of therapy to progression of disease and overall survival were calculated using Kaplan-Meier method. Results and limitations The median age in the cohort was 28 years (range 12–72), and all patients tested had sickle cell trait. Overall survival was 5.8 months (95% CI 4.1–10.9) and for 12 patients who received platinum-based therapy, median progression-free survival was 2.5 months (95% CI 1.2-Not Reached). A total of 10 available tumors underwent analysis with fluorescence in situ hybridization for SMARCB1; this revealed loss of heterozygosity with concurrent translocation in 8, and biallelic loss in 2. Next-generation targeted sequencing showed no recurring mutations. Conclusions Outcome was generally poor in this cohort of patients with RMC. Uniform loss of SMARCB1 is a key molecular feature in this tumor and mechanism of loss appears to be mostly through translocations and deletions.

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Section: Discussionmentioning

confidence: 94%

Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes

Carlo

Chaim

Patil

et al. 2017

Clinical Genitourinary Cancer

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“…[7] In brief, formalin-fixed, paraffin-embedded slides or blocks from tumor samples were subjected to comprehensive genomic profiling (CGP) in a CLIA-certified, CAP-accredited, NYS-regulated reference laboratory (Foundation Medicine, Inc.). At least 50 ng of DNA per specimen was extracted and next-generation sequencing was performed on hybridization-captured, adaptor ligation based libraries to high, uniform coverage (>500×) for all coding exons of 182-315 cancer-related genes and 14-28 genes commonly rearranged in cancer.…”

Section: Methodsmentioning

confidence: 99%

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

Lara

Heilmann²,

Elvin³

et al. 2017

JCO Precision Oncology

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Background TMPRSS2-ERG gene fusions are frequently found in prostate cancer and are pathognomomic for prostatic origin. In a series of cancer cases assayed with comprehensive genomic profiling (CGP) in the course of clinical care, we reviewed the frequency of TMPRSS2-ERG fusions in patient tumors of various histologic subtypes. Methods Frequency of TMPRSS2-ERG fusions was determined in comprehensive genomic profiles from 64,263 cancer cases submitted to Foundation Medicine to assess genomic alterations suggesting benefit from targeted therapy. Genomic results from an index case of prostate cancer that underwent evolution from adenocarcinoma to pure squamous cell carcinoma are presented. Results TMPRSS2-ERG fusions were identified for 0.86% (250/29030) of male patients and not found for female patients (0/35233). TMPRSS2-ERG fusions were detected in six tumors that were classified as squamous carcinoma, five of which were of unknown primary site. The index case is a patient with a large left retrovesical mass diagnosed as squamous carcinoma by morphologic examination and a history of Gleason 9 prostate cancer with prior prostatectomy and salvage radiation therapy. TMPRSS2-ERG was detected by genomic profiling in the squamous cell tumor, the primary adenocarcinoma of the prostate, and in a metachronous prostatic adenocarcinoma metastasis. Based on these results, the patient received androgen deprivation therapy. A phylogenetic tree demonstrating clonal and histopathologic evolution of prostate cancer in the index patient was constructed. Conclusions In this large CGP dataset, TMPRSS2-ERG fusion was seen in ~30% of prostate cancers regardless of histologic type; the fusion was on occasion detected in advanced cancers not initially carrying a diagnosis of prostate carcinoma. CGP of advanced cancers in men may reveal prostatic origin by detection of the pathognomomic TMPRSS2-ERG fusion gene.

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“…Cytogenetic alterations and deletions (loss of heterozygosity) of chromosomes 1q, 8p, und 13q are described [34,35,36]. There is no distinct mutation that characterizes the subtype, but 29% of all patients present with mutations of NF2 and 24% with mutations of SETD2 [37]. …”

Section: Pathology and Molecular Alterationsmentioning

confidence: 99%

Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options

et al. 2019

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Non-clear cell renal cell carcinomas (nccRCC) are rare diseases with heterogeneous histopathologically and genetically defined entities. The clinical data on optimal systemic treatments of nccRCC is rather limited. In this review, the current World Health Organization (WHO) classification of nccRCC based on histopathologic and genetic findings is reported. Regarding systemic treatment options, the most commonly used agents are mTOR inhibitors like everolimus or temsirolimus, or tyrosine kinase inhibitors like sunitinib. 2 small randomized clinical trials with nccRCC comparing sunitinib with everolimus revealed a trend towards a better progression-free survival (PFS) and overall survival (OS) in favor of sunitinib. In RCC with predominant sarcomatoid features, both chemotherapy and targeted agents are reported without any preference for outcome. For subsequent lines of therapy, some case reports describe promising effects of PD-1 or PD-L1 inhibitors in nccRCC including sarcomatoid subtype and Bellini duct carcinoma. Currently, nccRCCs are treated similarly to clear cell RCC or, whenever possible, within clinical trials. Clinical trials with immune checkpoint inhibitors are ongoing.

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Characterization of Clinical Cases of Collecting Duct Carcinoma of the Kidney Assessed by Comprehensive Genomic Profiling

Cited by 96 publications

References 31 publications

Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes

Genomic Characterization of Renal Medullary Carcinoma and Treatment Outcomes

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

Non-Clear Cell Renal Cell Carcinoma - Pathology and Treatment Options

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